Preparation of 2,2-Difluoro-1-arylethenylstannane as a Precursor of 1,1-Diaryl-2,2-difluoroethenes

Abstract

gem-Difluoroolefins have attracted much attention because they show chemical reactivities toward nucleophiles 1,2 and are useful intermediate for the synthesis of fluorinated organic compounds via addition-elimination reaction.3 They are also important class of potential mechanism-based inhibitors 4 and have been known to behave as a bioisostere for carbonyl group. 5 The synthesis of gem-difluoroolefins can be mainly achieved by two generalized methods such as Wittig and related reaction, and metalation and related chemistry.6,7 However, Wittig methodology was not suitable for the preparation of 1,1-diaryl-2,2-difluoroethenes because of the poor reactivity of the diaryl ketones.8-11 One straightforward route to 1,1-diaryl-2,2-difluoroethenes is to use 2,2-difluoroethenylmetal reagents. Among these reagents, one of the promising precursors to gem-difluoroolefins is 2,2-difluoroethenylstannane reagents which can be utilized as cross-coupling reaction at stannyl site. Although numerous methods for the preparation of 2,2-difluoroethenylmetal reagents have been well documented in the previous literatures, 12-15 methods for the preparation of 2,2-difluoroethenylstannane reagents have been quite limited, in which 1,1-diaryl-2,2-difluoroethenes can be easily prepared by the Stille cross-coupling reaction. Percy et al. reported a method for the synthesis of 2,2-difluoro-1-tributylstannylethenyl diethylcarbamate from the reaction of 2,2-difluoro-1-lithioethenyl diethylcarbamate with tributylstannyl chloride. 16,172,2-Difluoro-1-tributylstannylethenyl ethers were prepared in a similar manner and their cross-coupling with aryl iodides, followed by cleavage of ether linkage provided difluoromethyl ketones.18,19 Burton et al. synthesized 2,2-difluoroethenylstannane from the reaction of 2,2-difluoroethenyltriethylsilane with tributylstannyl chloride in the presence of KF.20 He also prepared 2,2-difluoro-1-bromoethenylstannane from the reaction of 1,1-dibromo-2,2-difluoroethene with tributyltin chloride in the presence of Zn metal. 21 We reported a method for the preparation of 2,2-difluoro-1-phenylethenylstannane from the stannylation of sulfonyl group in 2,2-difluoro-1-phenylethenylsulfone and its arylation to give 1,1-diaryl-2,2-difluoroethenes.22 Alkenylation and alkynylation of 2,2-difluoro-1-phenylethenylstannane provided the corresponding 1,1-difluoro-1,3-butadienes 23 and 1,1-difluoro-1,3-enynes.24 Recently, efficient synthesis of 2,2-diaryl-1,1-difluoroethenes can be achieved by consecutive cross-coupling reactions of 2,2-difluoro-1-tributylstannylethenyl ptoluenesulfonate.25 However, a general preparation of 1-aryl-2,2-difluoroethenylstannane which is a better coupling partner of arylation as compared to 1-aryl-2,2-difluoroethenyltosylate 25 has not been reported in the previous liternature. Herein, we wish to report a general method for the preparation of 1-aryl-2,2-difluoroethenylstannane which should be a nice precursor to 1,1-diaryl-2,2-difluoroethenes.2,2-Difluoro-1-tributylstannylethenyl p-toluenesulfonate (1) w...

Cross-Coupling Reactions of Double or Triple Electrophilic Templates for Alkene Synthesis

“…The same group also reported the simple stannylation of 2,2-difluoro-1-phenylethenyl p-toluenesulfonate en route to (2,2-difluoro-1-phenylethenyl)tributylstannane. 21 Previously published results indicate that the order of reactivity of the halovinyl tosylates in cross-coupling reactions is as follows: F, Cl < OTs < Br, I. However, a series of recently published papers described the unusual behavior of difluorovinyl tosylate during C-H activation experiments.…”